Search

Objective: To explore the impact of textbook outcome (TO) on long‐term survival in oral cancer surgery. Subjects and Methods: In total, 386 patients with tumor resection, neck dissection (ND), and reconstruction between 2011 and 2020 were included. TO was defined as negative margin; adequate ND; no 3‐day emergency room revisit; no 30‐day readmission; and length of stay ≤22 days. Multivariate Cox regression was used to evaluate the impact of TO and 5‐year overall survival (OS). Results: The TO rate was 35%. Younger age, subsite in buccal area, Charlson Comorbidity Index Score of 0, higher body mass index, higher hemoglobin, higher albumin, and unilateral ND were associated with TO. 5‐year OS was 70.5% in overall TO patients and 49.0% in non‐TO patients (HR, 0.47; 95% CI, 0.31–0.70; p < 0.001). Non‐TO was associated with an increased mortality rate (aHR, 1.73; 95% CI, 1.14–2.63) after adjusting other factors and the result remained robust with inverse probability of treatment weighting analysis. The impact of TO on OS was more significant in age <60, advanced stage, and diagnosis year before 2018. Conclusion: Not achieving TO in oral cancer surgery was associated with worse long‐term outcome. TO could be used as a proxy for surgical quality improvement. [ABSTRACT FROM AUTHOR]

Background: This study aimed to establish a simple predictive model for oropharyngeal cancer (OPC) in an area with a relatively low prevalence of human papillomavirus (HPV) and frequent betel nut chewing. Methods: A total of 116 patients with OPC were recruited from the clinical research database of a referral cancer center between 2013 and 2018. Patient characteristics—including age, gender, tumor stage, differentiation, and treatment modality—were extracted from the database. Patients diagnosed after 2018 were staged using the 7th AJCC staging system to explore the impact of extra-nodal tumor extension (ENE) on survival. Immunohistochemical analysis was performed for p16, epidermal growth factor receptor (EGFR), p53, and programmed cell death ligand 1 (PD-L1). ENE status was evaluated by pathological analysis or radiological features. Primary outcome was disease-specific overall survival (OS). Univariate and multivariate Cox regression were used to establish a predictive model. Results: Mean age was 57.3 ± 9.9 years; 103 patients (88.8%) were male. P16 positive OPC was positively associated with higher PD-L1 and a tonsillar sub-site and negatively associated with betel nut chewing and cigarette smoking. In Cox regression, age, p16 status, EGFR, cT4, ENE, and cigarette smoking were significantly associated with OS. In survival tree analysis, cT stage was the most important risk stratification parameter, followed by EGFR expression and p16 status. Patients with cT4 stage or high EGFR were classified as the high-risk group and had poorest OS. Conclusions: Due to the low prevalence of HPV and popularity of betel nut chewing in Asia, the relative importance of prognostic predictors for OPC are not identical to Western countries. Identification of significant prognostic biomarkers may improve treatment. Trial registration This study was registered and approved by the Institutional Review Board (IRB) of Kaohsiung Veterans General Hospital (VGHKS19-CT9-07; date of approval: Aug 9, 2019). [ABSTRACT FROM AUTHOR]

Objective: Haptoglobin (Hp) is an acute-phase protein secreted by the liver; its concentration increases rapidly during infection, inflammation, and tumor formation. It has been reported that the level of Hp α alleles is altered in the serum of patients with head and neck squamous cell carcinoma (HNSCC), and the cellular level of Hp is strongly associated with the recurrence rate of HNSCC in patients. In the present study, the regulated mechanism of Hp expression was explored.Materials and Methods: We first identified the genetic polymorphism of Hp by PCR. The expression of Hp isoforms was determined through Western Blotting analysis. With the JAK specific inhibitors, the clear regulation mechanism was explored.Results: We observed that Hp exhibited variant polymorphisms in different cells. We found that interleukin-6 (IL-6) induced the expressions of Hp α2 in FaDu cells, and Hp α1 in SCC4 cells. Furthermore, the phosphorylated level of STAT3 was elevated with IL-6 treatment. Janus-associated kinase 2 (JAK-2) inhibitor, WP1066, reduced the phosphorylation of STAT3 after IL-6 induction, leading to the downregulation of Hp expression.Conclusions: The expression of Hp was increased via IL-6 induction through the activation of the transcription factor STAT3 in HNSCC cells. [ABSTRACT FROM AUTHOR]

Objective: In Taiwan, the median age of diagnosis for oral cavity cancer is 51 year old, which is about 10 years earlier than that in Western countries. A recent study assessing the effect of marriage on outcomes for elderly oral cavity cancer patients (≥66 years old) showed that marriage was associated with better survival. However, little is known about the prognostic significance of marital status in oral cavity cancer patients aged 65 years and younger.Methods: Data from 2007 to 2014 were collected from the Cancer Registry Dataset of the Kaohsiung Veterans General Hospital. We reviewed the records of all newly diagnosed patients with oral cavity cancer who were aged 65 years and younger and being treated by primary surgery with or without neck dissection or adjuvant therapy. None of the included patients had distant metastasis upon diagnosis. In total, 457 patients were indentified. We used multivariate Cox regression model to evaluate the effect of marriage on disease-specific survival rates after adjusting for demographic variables and treatments.Results: There was no significant difference between the married and unmarried groups in stage at diagnosis or treatment. The 5-year disease-specific survival was 70.9% in the married group and 51.2% in the unmarried group (P=0.001). Multivariate analysis with Cox regression showed that unmarried patients had worse disease-specific survival (unmarried, adjusted hazard ratio [aHR] 1.51, 95% CI: 1.06-2.16). Subgroup analysis among patients stratified by the independent factors in multivariate analysis revealed that being unmarried was associated with a trend of worse survival in most stratified groups.Conclusion: Marriage was associated with better disease-specific survival for oral cavity cancer patients aged 65 years and younger. [ABSTRACT FROM AUTHOR]

Objective: Several comorbid measures have been developed and demonstrated the predictive ability for cancer mortality. We conducted a retrospective study on oral squamous cell carcinoma (OSCC) patients to compare the Charlson comorbidity index score (CCIS) to the Elixhauser comorbidity index score (ECIS).Methods: Newly diagnosed OSCC patients (n=232) post major surgery with or without adjuvant therapy were identified from the cancer registry database between 2006 and 2011. Comorbidities present prior to the cancer diagnosis were obtained and adapted to the CCIS and ECIS. The prevalence of comorbid conditions and the influence on disease-specific survival (DSS) rate were calculated and analyzed by Cox regression model. The discriminatory ability of these two comorbid measures was evaluated by using the adjusted hazard ratio and Akaike information criterion (AIC) in a multivariate regression model. The prediction accuracy was assessed using Harrell's c-statistic.Results: Most of the patients (93.5%) were male with a mean age of 54 ± 11 years and 77 of them (33.1%) had at least one comorbid condition. The ECIS was associated DSS, with an additional 10% increased risk observed for mortality for each increased score (HR, 1.10; 95% confidence interval [CI], 1.03-1.18) after adjusting with pathological risk features. However, the CCIS was not an independent prognostic factor for these patients. The ECIS increased discriminatory ability but the CCIS did not improve discrimination.Conclusions: Comorbid conditions significantly influenced the clinical outcomes of patient with OSCC post major surgery. A higher ECIS was associated with worse disease specific survival indicative of a valuable prognostic indicator. The ECIS may be considered in further clinical trials for a variety of cancers, including head and neck cancers. [ABSTRACT FROM AUTHOR]

Objective: This population-based study investigated the subsequent cardiovascular risk of patients with knee osteoarthritis underwent total knee arthroplasty in Taiwan. Materials and methods: This was a population-based follow-up study of 22931 patients diagnosed with knee osteoarthritis between 2008 and 2011. Each patient was followed for 3 years or until death. Treatment was dichotomized into conservative treatment and TKA. The association between TKA and cardiovascular disease (CVD) events was analyzed using propensity score analysis and instrumental variable analysis and two-stage least-squares regression model. Results: Patients with knee osteoarthritis who underwent TKA had a lower 3-year cumulative risk of stroke and acute myocardial infarction (AMI). After adjusting for measured risk and confounding factors, propensity score showed a 0.56 fold (adjusted OR = 0.56; 95% CI, 0.51–0.61; p<0.001) risk for CVD in those with TKA. Use of instrumental variable analysis for adjusting measured and unmeasured factors and two-stage least squares regression model revealed that the average treatment effect of TKA was statistically associated with a decreased 7% risk of CVD events (95% CI, 0.2%–13.6%). Conclusion: Our study revealed that patients with knee osteoarthritis who underwent TKA had a lower risk of suffering from a future severe cardiovascular event. This benefit may be attributed to an improvement in physical activity, reduction of psychosocial stress, and/or a decreased use of NSAIDs as a result of having undergone TKA. [ABSTRACT FROM AUTHOR]

Background: To investigate the association of basic demographic data, socioeconomic status, medical services, and hospital characteristics with end-of-life expenditure in patients with oral cancer in Taiwan who died between 2009 to 2011. Methods: This nationwide population-based, retrospective cohort study identified 5,386 patients who died from oral cancer. We evaluated medical cost in the last month of life by universal health insurance. The impact of each variable on the end-of-life expenditure was examined by hierarchical generalized linear model (HGLM) using a hospital-level random-intercept model. Results: The mean medical cost in the last six months of life was $2,611±3,329 (U.S. dollars). In HGLM using a random-intercept model, we found that patients younger than 65 years had an additional cost of $819 over those aged ≥65 years. Patients who had a high Charlson Comorbidity Index Score (CCIS) had an additional $616 cost over those with a low CCIS. Those who survived post-diagnosis less than 6 months had an additional $659 in expenses over those who survived more than 24 months. Medical cost was $249 more for patients who had medium to high individual SES, and $319 more for those who were treated by non-oncologists. Conclusion: This study provides useful information for decision makers in understanding end-of-life expenditure in oral cancer. We found significantly increased end-of-life expenditure in patients if they were younger than 65 years or treated by non-oncologists, or had high CCIS, medium to high individual SES, and survival of less than 6 months after diagnosis. [ABSTRACT FROM AUTHOR]

Objective The aim of the study is to explore the incidence and the risks associated with major osteoporotic fractures, all-cause mortality with osteoporotic fractures and the effect of the psychiatric drug exposure in patients with schizophrenia during a 10-year follow-up period. Methods Two nationwide cohorts were selected from the Taiwan National Health Insurance Research Database (NHIRD) consisting of 30,335 patients with schizophrenia (age ≥ 40 years) and 121,340 age- and sex-matched control participants without schizophrenia. The psychiatric proportion of days covered (PDC) is an indicator of the intensity of drug exposure in patients with schizophrenia. The incidence and risk factors of major osteoporotic fractures were calculated for both cohorts. Additionally, the patient survival rate after major osteoporotic fractures was also calculated. Results During a 10-year follow-up period, 1677 (5.53%) schizophrenia and 4257 (3.51%) control subjects had major osteoporotic fractures (P < 0.001). The schizophrenia patients with a PDC > 0.1 showed a significantly higher incidence of major osteoporotic fractures than did the non-schizophrenia controls; however, those with a psychiatric PDC ≤ 0.1 did not. After adjustment, the psychiatric PDC was significantly and independently associated with the risk of major osteoporotic fractures except some medical morbidities but the schizophrenia diagnosis was not. In addition, among all 5934 patients with major osteoporotic fracture, the adjusted mortality hazard ratio for psychiatric PDC was 1.92 (95% CI = 1.63–2.26). Conclusions Patients with schizophrenia are at a higher risk for major osteoporotic fractures than the general population and also have a higher mortality rate due to major osteoporotic fractures. These findings may be caused by psychiatric drug use rather than schizophrenia, which suggests that directions can be taken in future studies. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 37-year-old man with left-sided middle ear effusion (MEE). Examinations showed smooth nasopharyngeal mucosa without tumor lesions, and a cystic mass lesion that is infratemporal fossa with likely proteinaceous fluid content. He underwent nasopharyngeal navigator-assisted endoscopic marsupialization that also revealed an epithelial lining cyst. The patient remained asymptomatic and MEE free at the 10-month follow-up.

Background: The aim of this study was to determine the influence of inflammation on acute phase protein and epithelial-mesenchymal transition (EMT) in buccal cancer. Methods: Western blotting was carried out to investigate the expression of haptoglobin and epithelial-mesenchymal transition in oral cancer cell lines with or without IL-6 stimulation. We studied patients with buccal cancer patients without distant metastasis at diagnosis. Correlation between cellular haptoglobin, EMT, and clinical characteristics of buccal cancer was analyzed to assess the prognostic value of cellular haptoglobin level and EMT. The relationship of haptoglobin, and EMT expression with survival was assessed using Cox proportional hazard models. Results: Western blotting analysis showed that increased haptoglobin protein was associated with overexpression of vimentin. Under IL-6 stimulation, overexpression of haptoglobin, EMT-associated motile phenotype was noted in OC2 cell lines. Overexpression of haptoglobin was also associated with an increased risk for locoregional recurrence [hazard ratio (HR) 1.04; p=0.011] after adjusting for age, gender, disease site, stage, and treatment modality. Conclusions: Increased cellular expression of haptoglobin is associated with EMT in oral cancer cell lines and this phenomenon could be exaggerated with IL-6. Cellular expression of haptoglobin is related to locoregional recurrence rate in buccal cancer patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This study aimed to estimate the incidence and relative risk of stroke and post-stroke all-cause mortality in patients with schizophrenia. Methods: This study identified a study population from the National Health Insurance Research Database (NHIRD) between 1999 and 2003 that included 80,569 patients with schizophrenia and 241,707 age- and sex-matched control participants without schizophrenia. The participants were randomly selected from the 23,981,020-participant NHIRD, which consists of 96% Taiwanese participants. Participants who had experienced a stroke between 1999 and 2003 were excluded. Using data from the NHIRD between 2004 and 2008, the incidence of stroke (ICD-9-CM code 430-438) and patient survival after stroke were calculated for both groups. After adjusting for confounding risk factors, a Cox proportional-hazards model was used to compare the five-year stroke-free survival rate to the all-cause mortality rate across the two cohorts. Results: Over five years, 1380 (1.71%) patients with schizophrenia and 2954 (1.22%) controls suffered from strokes. After adjusting for demographic characteristics and comorbid medical conditions, patients with schizophrenia were 1.13 times more likely to have a stroke (95% CI=1.05–1.22; P=0.0006). In addition, 1039 (24%) patients who had a stroke died during the follow-up period. After adjusting for patient, physician and hospital variables, the all-cause mortality hazard ratio for patients with schizophrenia was 1.23 (95% CI=1.06–1.41; P=0.0052). Conclusions: During a five-year follow-up, the likelihood of developing a stroke and the all-cause mortality rate were greater among patients with schizophrenia as compared with the control group. [Copyright &y& Elsevier]

Summary: This population-based study investigated the relationship between individual and neighborhood socioeconomic status (SES) and oral cancer mortality. A population-based follow-up study was conducted of 3607 oral cancer patients (predominantly male) who were diagnosed between 2004 and 2005. Each patient was traced to death or for 2years. Individual SES was defined by enrollee category. Neighborhood SES was defined by income, and numbers of doctors, and neighborhoods were grouped into advantaged and disadvantaged areas. The Cox proportional hazards model was used to compare the death-free survival rate between the different SES groups after adjusting for possible confounding and risk factors. In oral cancer patients aged below 65years, death rates among those with low SES were highest in disadvantaged neighborhoods. After adjusting for patient characteristics (age, gender, Charlson Comorbidity Index Score, urbanization, and area of residence), tumor extent, treatment modalities (operation, adjuvant therapy), hospital characteristics (ownership, teaching level, caseload), and year of diagnosis, oral cancer patients with low individual SES in disadvantaged neighborhoods conferred a 1.46- to 1.64-fold higher risk for death, compared with patients with high individual SES in advantaged neighborhoods. No statistically significant difference was found in risk of death between different SES groups in patients aged 65 and above. Our findings indicate that oral cancer patients with low individual SES have the highest risk of mortality even under a universal health-care system. Public health strategies and welfare policies must continue to focus on this vulnerable group. [Copyright &y& Elsevier]

Background: Positive correlation between caseload and outcome has previously been validated for several procedures and cancer treatments. However, there is no information linking caseload and outcome of nasopharyngeal carcinoma (NPC) treatment. We used nationwide population-based data to examine the association between physician case volume and survival rates of patients with NPC.Methods: Between 1998 and 2000, a total of 1225 patients were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity score were used to assess the relationship between 10-year survival rates and physician caseloads.Results: As the caseload of individual physicians increased, unadjusted 10-year survival rates increased (p < 0.001). Using a Cox proportional hazard model, patients with NPC treated by high-volume physicians (caseload ≥ 35) had better survival rates (p = 0.001) after adjusting for comorbidities, hospital, and treatment modality. When analyzed by propensity score, the adjusted 10-year survival rate differed significantly between patients treated by high-volume physicians and patients treated by low/medium-volume physicians (75% vs. 61%; p < 0.001).Conclusions: Our data confirm a positive volume-outcome relationship for NPC. After adjusting for differences in the case mix, our analysis found treatment of NPC by high-volume physicians improved 10-year survival rate. [ABSTRACT FROM AUTHOR]

Abstract: Background: We determined whether expression of haptoglobin by head and neck squamous cell carcinoma (HNSCC) cells is associated with prognosis. Methods: Western blotting was carried out to investigate the expression of haptoglobin in oral cancer cell lines. We study patients with HNSCC without distant metastasis at diagnosis. Correlation between cellular haptoglobin and clinical characteristics of HNSCC was analyzed to assess the prognostic value of cellular haptoglobin level. Kaplan–Meier survival curves and log-rank test were used to evaluate differences in recurrence, distant metastasis, and overall survival rates between patients grouped according to cellular haptoglobin level in cancer tissues. The relationship of haptoglobin expression with survival was assessed using Cox proportional hazard models. Results: Western blotting analysis showed that haptoglobin protein was expressed in 4 oral cancer cell lines. The recurrence rate was higher in HNSCC patients with over-expression of haptoglobin (>50%) (P =0.045). Over-expression of haptoglobin was also associated with an increased risk for recurrence (hazard ratio [HR] 3.2; 95% confidence interval [CI], 1.127–8.895; P =0.029) after adjusting for age, gender, disease site, stage, and treatment modality. Conclusions: Altogether, the data presented show that cellular expression of haptoglobin is closely related to recurrence rate in HNSCC patients. The elevated risk of relapse was confirmed in a multivariate analysis. The cellular expression of haptoglobin may be a prognostic factor in HNSCC. [Copyright &y& Elsevier]

Summary: Patients with oral cancer utilize considerable health care resources, particularly when wide resection of the tumor and reconstruction with pedicle flap/free flap is performed. This study was conducted to explore the relationship between survival rates and surgeon volume. A total of 1256 patients who underwent resections for oral cancer in 2005 were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional regression model, and propensity score were used to evaluate the association between 3-year survival rates and surgeon caseloads. Oral cancer patients treated by high-volume surgeons (caseload 22–117) had better survival rates (hazard ratio [HR]=0.656; 95% confidence interval [CI], 0.484–0.89; P =0.007) using the Cox proportional regression model after adjusting for patients’ comorbid conditions, hospital, and surgeon characteristics. When analyzed by propensity score, the adjusted 3-year survival rate was 74% for patients treated by high-volume surgeons compared to 58% in the low/medium-volume group (P =0.019). We concluded that for patients who underwent oral cancer resection and reconstruction, after adjusting for differences in the case mix, high-volume surgeons had better 3-year survival rates. Treatment strategies adopted by high-volume surgeons should be analyzed further and utilized more widely. [Copyright &y& Elsevier]

Abstract: Objectives: To evaluate the impact of invasion of the prevertebral or parapharyngeal spaces and large tumor volume on treatment outcomes in patients with nasopharyngeal carcinoma (NPC). Methods: A total of 105 patients with newly diagnosed NPC were enrolled in this study. TNM stage and presence of invasion of the prevertebral or parapharyngeal spaces were recorded. All patients received a total dose of 70–75Gy. Results: After controlling for age, sex, and chemotherapy status, invasion of the prevertebral or parapharyngeal spaces and large primary tumor volume produced a significantly increased hazard ratio for distant metastasis and recurrence. We defined patients with two or more such prognostic factors as high-risk patients, in whom the 3-year metastasis-free survival rate, with and without adjuvant chemotherapy, was 100% and 69.6%, respectively (P =0.02). Their 3-year recurrence-free survival rate, with and without adjuvant chemotherapy, was 93.3% and 70.2% (P =0.09). This benefit was not observed in low-risk NPC patients. Conclusion: NPC patients with any two or more of the factors, involvement of the prevertebral space, large primary tumor volume, or advanced parapharyngeal space invasion, had more recurrence and poor survival rates and benefited from concurrent chemoradiotherapy followed by adjuvant chemotherapy. [Copyright &y& Elsevier]

Abstract: Objectives: To elucidate the effect of primary tumor volume (PTV) on treatment outcomes in patients with nasopharyngeal carcinoma (NPC) who were treated with radiotherapy or concurrent chemoradiotherapy. The TNM staging system developed by American Joint Committee of Cancer (AJCC) is universally used and accepted but its prediction of prognosis in NPC receives a lot of challenge. Primary tumor volume had been reported to have close relationship with prognosis of head and neck cancer. We may predict prognosis of NPC with PTV. Methods: From 1999 to 2006, 91 patients with newly diagnosed NPC who were treated with radiotherapy or CCRT were enrolled in the study. Computed tomography-derived or magnetic resonance-derived primary tumor volume was calculated. The correlation between AJCC disease stage, primary tumor volume and disease-specific survival were analyzed. Multivariate analyses using the Cox proportional hazard model was performed. Results: The median primary tumor volume for the whole series was 11.39ml (range 1.25–166.58ml). The median primary tumor volume was 2.69ml in T1 disease, 10.14ml in T2 disease, 15.41ml in T3 disease, and 26.69ml in T4 disease. Hazard ratio increased with tumor volume, ranging from 5.91 (95% confidence interval (95% CI) 1.13–26.43) for tumor volumes between 20ml and 40ml, and 15.72 (95% CI, 3.82–61.05) for tumor volumes >40ml. With both tumor volume and T classification in the same Cox regression model, only tumor volume remained statistically significant in the prognosis of NPC. Conclusion: Primary tumor volume has closer relationship with survival rates of patients with NPC. Calculation of primary tumor volume may be further considered to improve the current staging system. [Copyright &y& Elsevier]

Conclusions. Primary tumor volume (PTV) has a close relationship with survival rates of patients with nasopharyngeal carcinoma (NPC) who were treated with concurrent chemoradiotherapy (CCRT) or radiotherapy. Besides the current AJCC staging system, measurement of PTV may be needed to predict prognosis of NPC and adjust treatment strategy. Objectives. We conducted a retrospective study to elucidate the effect of PTV on treatment outcomes in patients with NPC who were treated with CCRT or radiotherapy. Patients and methods. A total of 66 patients with newly diagnosed NPC were enrolled in this study. Computed tomography (CT)-derived or magnetic resonance imaging (MRI)-derived PTV was calculated. The correlation between AJCC disease stage, PTV, and disease-specific survival was analyzed. Correlations between different prognostic factors were assessed using a Cox regression model. Results. The median PTV for the whole series was 12.01 ml (range 1.25-166.58 ml). The median PTV was 3.45 ml in T1 disease, 7.96 ml in T2 disease, 17.95 ml in T3 disease, and 64.73 ml in T4 disease. Disease stage and T stage carried no prognostic significance (p=0.25 and p=0.30, respectively). Four categories of PTV (<12.5 ml, 12.5-25 ml, 25-50 ml and >50 ml) had prognostic significance (p=0.02). Survival analysis demonstrated a significant difference in overall survival with larger tumor volume (risk ratio 5.447; p=0.044). [ABSTRACT FROM AUTHOR]

Conclusions. Young patients with squamous cell carcinoma (SCC) of the oral tongue developed fewer locoregional recurrences. The overall survival and disease-specific survival rates were better in the young patient population. Objectives. To compare the survival rates of patients under 45 years of age and diagnosed with SCC of the oral tongue with those of patients older than 45 years. Patients and methods. A retrospective review of 20 patients under 45 years of age with SCC of the oral tongue was performed. These patients were matched to an older population by sex and clinical stage. Overall survival, disease-free survival, disease-specific survival, and rates of local, regional and distant metastases were determined for both populations. Results. Stage and treatment modality were similar in the two age groups. There were significant differences in overall survival (p=0.013) and disease-specific survival (p=0.046) favoring young patients. Rates of locoregional recurrence and distant metastasis were higher in the older patients. [ABSTRACT FROM AUTHOR]

Background: Adaptive radiotherapy (ART) has potential benefits in patients with nasopharyngeal cancer (NPC). This retrospective study aimed to identify the factors favoring ART.Materials and Methods: Forty NPC patients were retrospectively included in this study. All patients received two-phase, volumetric modulated arc radiotherapy (VMAT) and underwent a second computed tomography (CT) for the phase II ART. We generated phantom, non-ART plans by a hybrid method for comparison with ART plans. A paired t-test was used to evaluate the dose differences between these two plans. A subgroup analysis through a paired t-test was used to evaluate the factors favoring ART.Results: The second CT images were captured at the median 22 fractions. The median total dose of the planning target volume-one (PTV-1) was 72 Gy, and the phase II dose was 16 Gy. The volumes of the ipsilateral parotid gland (23.2 vs. 19.2 ml, p <  0.000), contralateral parotid gland (23.0 vs. 18.4 ml, p <  0.000), clinical target volume-1 (CTV-1, 32.2 vs. 20.9 ml, p <  0.000), and PTV-1 (125.8 vs. 107.3 ml, p <  0.000) all shrunk significantly between these two CT simulation procedures. Among the nearby critical organs, only the ipsilateral parotid gland displayed significant dose reduction by the ART plan (5.3 vs. 6.0 Gy, p = 0.004). Compared to the phantom plan, the ART could significantly improve the PTV-1 target volume coverage of D98 (15.4 vs. 12.3 Gy, p < 0.000). Based on the D98 of PTV-1, the factors of a large initial weight (> 60 kg, p < 0.000), large body mass index (BMI) (> 21.5, p < 0.000), obvious weight loss (> 2.8 kg, p < 0.000), concurrent chemoradiotherapy (p < 0.000), and stages III-IV (p < 0.000) favored the use of ART.Conclusions: ART could significantly reduce the mean dose to the ipsilateral parotid gland. ART has dosimetrical benefit for patients with a heavy initial weight, large BMI, obvious weight loss, concurrent chemoradiotherapy, and cancer in stages III-IV. [ABSTRACT FROM AUTHOR]

Purpose: Radiation/chemoradiotherapy-induced carotid stenosis and cerebrovascular events in patients with nasopharyngeal carcinoma (NPC) can cause severe disability and even death. This study aimed to estimate the risk of ischemic stroke in this patient population over more than 10 years of follow-up. Methods and Materials: The study cohorts consisted of all patients hospitalized with a principal diagnosis of NPC (n = 1094), whereas patients hospitalized for an appendectomy during 1997 and 1998 (n = 4376) acted as the control group and surrogate for the general population. Cox proportional hazard model was performed as a means of comparing the stroke-free survival rate between the two cohorts after adjusting for possible confounding and risk factors. Results: Of the 292 patients with ischemic strokes, 62 (5.7%) were from the NPC cohort and 230 (5.3%) were from the control group. NPC patients ages 35–54 had a 1.66 times (95% CI, 1.16–2.86; p = 0.009) higher risk of ischemic stroke after adjusting for patient characteristics, comorbidities, geographic region, urbanization level of residence, and socioeconomic status. There was no statistical difference in ischemic stroke risk between the NPC patients and appendectomy patients ages 55–64 years (hazard ratio = 0.87; 95% CI, 0.56–1.33; p = 0.524) after adjusting for other factors. Conclusions: Young NPC patients carry a higher risk for ischemic stroke than the general population. Besides regular examinations of carotid duplex, different irradiation strategies or using new technique of radiotherapy, such as intensity modulated radiation therapy or volumetric modulated arc therapy, should be considered in young NPC patients. [Copyright &y& Elsevier]

Background: This study aimed to determine whether drug doses per kilogram of lean body mass (LBM) were associated with dose-limiting toxicity (DLT) events in head and neck cancer (HNC) patients.Methods: This retrospective cohort study included 179 HNC patients who underwent induction chemotherapy (IC) at a medical center from May 1, 2014, to May 31, 2021. HNC patients' characteristics, tumor factors, IC regimen and dose, laboratory data, and body composition factors, including lean body mass (LBM) and skeletal muscle index (SMI), derived from CT, MRI, or PET scan images and drug dose per kilogram LBM were recorded. Dose-limiting toxicity (DLT) events were regarded as the primary outcome. Multivariate logistic regression was used to establish a novel risk score for DLT events by the abovementioned variables. The above-mentioned risk score was validated in another cohort.Results: The overall DLT events during the first cycle of IC for 179 HNC patients was 24%. After stratifying by gender, docetaxel per kilogram LBM > 2.52 mg/kg (adjusted odds ratio [aOR]: 3.18; 95% confidence interval [CI], 1.25-8.09), pre-treatment glutamic pyruvic transaminase (GPT) > 40 U/L (aOR, 2.61; 95% CI, 1.03-6.64), and history of chronic liver diseases (aOR, 3.98; 95% CI, 1.03-15.46) were significant variables in male HNC patients. The DLT events risk was categorized by summation of the above-mentioned risk factors for male HNC patients. Three risk groups were stratified by overall event of 17.6%, 25.8%, and 75%. The above-mentioned risk score had an acceptable discriminatory ability in another validation cohort.Conclusions: Among male HNC patients treated with IC, docetaxel per kilogram LBM more than 2.52 mg/kg, pre-treatment GPT > 40 U/L, and history of chronic liver disease were significant risk factors for DLT events. Identifying high-risk patients could help physicians prevent severe/fatal complications among HNC patients undergoing IC, especially for the male individuals. [ABSTRACT FROM AUTHOR]

This study explores the possible association between the risk of ischemic stroke and conjugated equine estrogen (CEE) use in women who are over 55 years old and have diabetes. Data from the National Health Insurance system of Taiwan were used to identify 428 women over 55 years old with diabetes who used CEE (0.625 mg daily) from 2003 to 2009. For comparison, 21026 women with diabetes who were from the same cohort and did not use estrogen were used as a control group, excluding patients with previous ischemic stroke at the baseline. The propensity score method was used to identify a 1:3 ratio for the matched cohort (n = 1284). Covariates used for propensity score-matching included age and comorbidities. Cox’s proportional hazard model was applied to estimate the relationship between CEE use and ischemic stroke. The overall incidence of ischemic stroke was significantly lower in patients using CEE than in the control group (0.9% compared with 3.0%, p = 0.016). Further analyses using Cox’s proportional hazard model revealed that after adjusting for age, comorbidities, socioeconomic status, urbanization, and other medications associated with ischemic stroke, a lower risk was present in patients with CEE use (hazard ratio: 0.34; 95% confidence interval: 0.12–0.97). Time of menopause could not be identified because of the nature of the database. CEE might decrease the risk of ischemic stroke in women with diabetes aged over 55 years, according to this population-based study. [ABSTRACT FROM AUTHOR]

Background: To determine the association of 30‐day readmission with weekend discharge and the number of holiday days during a hospital stay (holiday ratio). Methods: This retrospective cohort study used the clinical research database and cancer registry data of our hospital from January 1, 2011 to December 31, 2017. Patient characteristics, tumor factors, clinical laboratory data, and proxies of continuity of care, such as weekend discharge or holiday ratio (holiday days/total hospitalization days), received statistical analysis. Multivariate logistic regression identified the independent factors for 30‐day potentially avoidable readmission rate (PAR). Results: Of 1433 patients receiving tumor resection, 520 (36.29%) had colon cancer; 440 (30.70%) had head and neck cancer (HNC), and 473 (33.01%) had other cancers (lung, liver, and prostate). The rate of 30‐day PAR was 6.3% for those with colon cancer, 8.6% for HNC, and 3.6% for other cancers. The 30‐day PAR did not significantly differ by discharge on a weekend versus weekday for those with colon cancer (8.33% vs. 5.90%; p = 0.379), HNC (7.06% vs. 9.01%; p = 0.566), or other cancers (0.00% vs. 4.28%; p = 0.960). Colon cancer patients with holiday ratio >0.3 had a higher readmission rate (9.58% vs. 4.82%, p = 0.041). In multivariate analysis, a holiday ratio >0.3 (adjusted odds ratio 2.16; 95% Confidence Interval, 1.05–4.39) in those with colon cancer was an independent predictor of 30‐day PAR. Conclusions: Weekend discharge after major surgery did not affect 30‐day readmission rates in cancer patients, but the holiday ratio did affect 30‐day PAR for those with colon cancer. [ABSTRACT FROM AUTHOR]

Objective: This study investigates the relationship between individual and neighborhood socioeconomic status (SES) and mortality among patients with schizophrenia. Methods: A study population was identified from the National Health Insurance Research Database (NHIRD) prior to the end of 1999 that included 60,402 patients with schizophrenia. Each patient was tracked until death or to the end of 2009. Individual SESs were defined by enrollee category. Neighborhood SES was defined by enrollee category (as a proxy for occupation) and education, which were classified according to the conventions of Hollingshead. Neighborhoods were also grouped into advantaged and disadvantaged areas. The Cox proportional hazards model was used to compare the death-free survival rate between the different SES groups after adjusting for possible confounding factors and risk factors. Results: During the 10-year follow-up period, the mortality rates among high, moderate, and low individual SES groups were 12.22, 14.75, and 18.48 %, respectively ( P < 0.001). Schizophrenia patients with low individual SESs in disadvantaged neighborhoods had a risk of death that was 18-22 % higher than that of those with high individual SES in advantaged neighborhoods. The analysis of the combined effect of individual SES and neighborhood SES revealed that the death rates were highest among those with low individual SES and low neighborhood SES ( P < 0.001). Conclusions: Schizophrenia patients with low individual SES in disadvantaged neighborhoods have the highest risk of mortality despite a universal health-care system. Public health strategies and welfare policies must continue to focus on this vulnerable group. [ABSTRACT FROM AUTHOR]

Background: It is known that the risk of dementia in patients with moderate to severe traumatic brain injury (TBI) is higher. However, the relationship between mild traumatic brain injury (mTBI) and dementia has never been established. Objectives: We investigated the incidences of dementia among patients with mTBI in Taiwan to evaluate if there is higher risk compared with general population. Methods: We utilized a sampled National Health Insurance (NHI) claims data containing one million beneficiaries. We followed all adult beneficiaries from January 1, 2005 till December 31, 2009 to see if they had been diagnosed with dementia. We further identify patients with mTBI and compared their risk of dementia with the general population. Results: We identified 28551 patients with mTBI and 692382 without. After controlled for age, gender, urbanization level, socioeconomic status, diabetes, hypertension, coronary artery disease, hyperlipidemia, history of alcohol intoxication, history of ischemic stroke, history of intracranial hemorrhage and Charlson Comorbidity Index Score, the adjusted hazard ratio is 3.26 (95% Confidence interval, 2.69–3.94). Conclusions: TBI is an independent significant risk factor of developing dementia even in the mild type. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE) is a life-threatening condition that occurs as a complication of cervical cancer. The aim of this study was to evaluate the incidence of VTE in cervical cancer patients during a 5-year follow-up. Methods: The study analyzed data deposited between 2003 and 2008 in the National Health Insurance Research Database (NHIRD), provided by the National Health Research Institutes in Taiwan. Totally, 1013 cervical cancer patients after treatment and 2026 appendectomy patients were eligible. The Kaplan-Meier method and the Cox proportional hazards model were used to assess the VTE risk. Results: The 5-year cumulative risk for VTE was significantly higher in the cervical cancer group than in the control group (3.3% vs 0.3%, p<0.001). The hazard ratio for VTE was 10.14 times higher in the cervical cancer group than in the controls. The combined presence of more comorbidities was associated with a higher risk for VTE. Furthermore, cervical cancer patients without VTE had a significantly higher survival (75.3% vs 30.3%, p<0.001). Conclusions: The cumulative risk of VTE was significantly higher in cervical cancer patients, and these patients also had lower survival rates. Strategies to reduce these risks need to be examined. [ABSTRACT FROM AUTHOR]

This study aimed to create a prediction model with a radiographic score, serum, and cerebrospinal fluid (CSF) values for the occurrence of shunt-dependent hydrocephalus (SDHC) in patients with aneurysmal subarachnoid hemorrhage (aSAH) and to review and analyze literature related to the prediction of the development of SDHC. Sixty-three patients with aSAH who underwent external ventricular drain insertion were included and separated into 2 subgroups: non-SDHC and SDHC. Patient characteristics, computed tomography scoring system, and serum and CSF parameters were collected. Multivariate logistic regression was conducted to illustrate a nomogram for determining the predictors of SDHC. Furthermore, we sorted and summarized previous meta-analyses for predictors of SDHC. The SDHC group had 42 cases. Stepwise logistic regression analysis revealed 3 independent predictive factors associated with a higher modified Graeb (mGraeb) score, lower level of estimated glomerular filtration rate group, and lower level of CSF glucose. The nomogram, based on these 3 factors, was presented with significant predictive performance (area under curve = 0.895) for SDHC development, compared with other scoring systems (AUC = 0.764–0.885). In addition, a forest plot was generated to present the 12 statistically significant predictors and odds ratio for correlations with the development of SDHC. First, the development of a nomogram with combined significant factors had a good performance in estimating the risk of SDHC in primary patient evaluation and assisted in clinical decision making. Second, a narrative review, presented with a forest plot, provided the current published data on predicting SDHC. [ABSTRACT FROM AUTHOR]

Purpose: To compare the treatment outcome and severe late adverse effects (AEs) between conventional volume and dose (CVD) and simultaneously reduced volume and dose (SRVD) of clinical target volume treatments in patients with nasopharyngeal carcinoma.Methods and Materials: This retrospective cohort study enrolled patients with nonmetastatic stage II to IV nasopharyngeal cancer from a single institute. Survival endpoints and severe (≥grade 3) late AEs and comorbidity were compared between groups. The correlation of severe late AEs, comorbidity, and overall survival (OS) were evaluated using Kaplan-Meier and Cox regression methods.Results: From January 2012 to June 2017, this study enrolled 178 patients, 64 in the CVD group and 114 in the SRVD group. The 2 groups did not differ significantly in patient characteristics except for mean follow-up time (37.6 vs 48.8 months; P = .01). The SRVD group did not significantly differ from the CVD group in local control survival (82.0% vs 78.4%; P = .85), regional control survival (89.9% vs 86.0%; P = .62), or disease-free survival (76.4% vs 66.9%; P = .67). The SRVD group had significantly better OS (93.9% vs 67.0%; P < .001) and salvage survival (79.3% vs 20.7%; P < .01) and a significantly lower ratio of severe lung infection (1 of 113 vs 5 of 59; P = .02). The SRVD group had a significantly lower risk of mortality (hazard ratio [HR], 0.3; P = .03). The factors associated with a significantly higher risk of mortality were N3 (regional lymph node stage status of N3) (HR, 3.0; P = .02); comorbidities of diabetes, coronary artery disease, or chronic kidney disease (grades 2-3) (HR, 3.8; P = .009), and severe lung infection (HR, 6.3; P = .007).Conclusions: Simultaneously reduced volume and dose of clinical target volumes did not impair locoregional control or disease-free survival. The benefits of SRVD treatment may include significant reduction in severe late AEs, particularly lung infection, dysphagia, and xerostomia. However, additional studies with longer patient follow-up are required to confirm these benefits. [ABSTRACT FROM AUTHOR]

Background: To assess the benefit of postoperative radiotherapy in patients with pT1-2N1M0 oral and oropharyngeal cancer by the quality of neck dissection.Methods: In the Surveillance, Epidemiology, and End Results database, pT1-2N1M0 oral and oropharyngeal cancer patients treated by primary tumor resection and neck dissection with or without radiotherapy were included between 2004 and 2015. Univariate and multivariate analysis were used to explore the effect of adjuvant radiotherapy on 5-year overall survival (OS) and disease-specific survival (DSS) among different quality of neck dissection.Results: Of the 1765 patients identified, 1108 (62.8%) had oral cancer, 1141 (64.6%) were men, and 1067 (60.5%) underwent adjuvant radiotherapy. After adjusting for confounding factors, postoperative radiotherapy reduced the adjusted hazard ratio (aHR) of 5-year OS to 0.64 (95% confidence interval [CI] 0.49-0.84) in those with < 18 lymph nodes (LNs) removed, but not in those with 19-24 LNs removed (aHR 0.78; 95% CI 0.73-1.13), and in those with ≥ 25 LNs removed (aHR 0.96; 95% CI 0.75-1.24). For 5-year DSS, similar effect was observed. The adjusted hazard ratio was 0.66 (95% confidence interval, 0.45-0.97) in those with < 18 LNs. The protective effect was not seen in those with 18-24 LNs (aHR 1.07; 95% CI 0.59-1.96), and in those with ≥ 25 LNs (aHR 1.12; 95% CI 0.81-1.56). Sensitivity testing also showed a robust protective effect of postoperative radiotherapy in patients with < 18 LNs removed.Conclusion: Radiotherapy was associated with improved survival in pT1-2N1M0 oral and oropharyngeal cancer patients without adequate neck dissection. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the impact or survival of low skeletal muscle mass (SMM) among patients with oral squamous cell carcinoma (OSCC) undergoing primary surgery. Design: This study was a retrospective cohort study. Setting: Oral squamous cell carcinoma patients treated at our referral centre from April 2005 to March 2014 were examined. Participants: The cohort comprised 276 patients with OSCC undergoing primary surgery. Main outcome measures: Estimated SMM was measured by calculating the cervical skeletal muscle mass from a CT scan of the head and neck. The 5‐year overall survival (OS) and disease‐specific survival (DSS) were analysed using a multivariable Cox regression model. Results: There were 276 patients with a male‐to‐female ratio of 12:1. A low SMM (<47.5 cm2/m2) was associated with worse survival. After adjustment for other factors, the result remained robust for OS (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.14‐2.67) and disease‐specific survival (HR 1.67, 95% CI 1.04‐2.67). In the subgroup analysis, worse OS and DSS were particularly noted in male patients (HR = 1.90, 95% CI 1.22‐2.97; HR = 1.91, 95% CI 1.27‐3.19) and in those younger than 60 years of age (HR = 1.91, 95% CI 1.14‐3.22; HR = 2.12, 95% CI 1.23‐3.64) with low SMM. Conclusions: Low SMM was a significant independent factor that was associated with lower survival in patients who have oral cavity cancers and are undergoing primary surgery. Preoperative CT scans of the head and neck could be utilised to evaluate SMM, predict treatment outcomes and facilitate nutrition management. [ABSTRACT FROM AUTHOR]

Objectives: To assess the impact of age on the survival of patients with head and neck squamous cell carcinoma (HNSCC) using different statistical methods. Design: A retrospective population‐based study. Setting: Surveillance, Epidemiology, and End Results database. Subjects and methods: A total of 28 639 patients with newly diagnosed HNSCC were enrolled between 1 January 2007 and 31 December 2013. The effect of age on 5‐year disease‐specific survival was calculated using a Kaplan‐Meier method and compared using log‐rank tests. A Cox proportional hazards model was used for a multivariate analysis. A classification and regression tree (CART) analysis that partitioned patients with significantly different Kaplan‐Meier curves was introduced to identify the important cancer‐related parameters influencing survival. Results: Uni‐ and multivariate analyses indicated that patients who were older than 60 years had poorer 5‐year disease‐specific survival regardless of tumour subsite and tumor‐node‐metastasis (TNM) stage. However, the CART analysis determined that age played only a minor role in survival after comparing with other prognosticators. The relative importance of age using the Gini index was as follows: 3.21% for oral cancer, 8.32% for oropharyngeal cancer, 2.56% for hypopharyngeal cancer and 16.51% for laryngeal cancer. Conclusions: Different to traditional statistical methods, the CART analysis which was used to identify homogeneous populations revealed that the impact of age varied for different patient groups according to the presence or absence of other prognosticators. This important information could help to guide our clinical decisions and future researches. [ABSTRACT FROM AUTHOR]

Objective: We examined whether dynamic margin criteria margin‐to‐thickness (MTR) ratio has superior predictive value compared with the resection margin or tumour thickness alone in the survival outcome in oral squamous cell carcinoma (OSCC). Design: This is a retrospective cohort study. Setting: Oral squamous cell carcinoma patients treated in Kaohsiung Veterans General Hospital Cancer Center between January 2006 and December 2013. Participants: A cohort of 302 patients with OSCC who had undergone surgical management. Main Outcomes Measures: Log MTR was calculated for each patient, and survival data were analysed using a multivariable Cox regression model. Discriminative analysis was performed using chi‐square, Akaike information criterion (AIC) and Harrell's C tests. Results: After assessing for discriminative ability, the linear trend of log MTR surpassed those of resection margin and tumour thickness in chi‐square, AIC and Harrell's C tests for the advanced pathologic T (pT) category. A multivariate Cox proportional hazard regression model revealed that log MTR <33% was associated with less favourable 5‐year disease‐specific survival (DSS) (P = 0.006) in the entire oral cancer study cohort. Other significant factors included perineural invasion (P = 0.021), pT category, (P = 0.005), pathologic N category (P < 0.001) and differentiation category (P = 0.022). Conclusions: Log MTR < 33% may be a predictor of less favourable outcome in the DSS of OSCC. Log MTR outperformed both resection margin and tumour thickness alone in terms of discriminative analysis. Our study could help in presurgical planning for high‐risk patients and in aiding the decision‐making process for adjuvant treatment. [ABSTRACT FROM AUTHOR]

Purpose: Diabetes mellitus (DM) is a global pandemic metabolic disorder. In recent years, the amount of medical resources required for the treatment of diabetes has increased as diabetes rates have gradually risen. The combined effects of individual and neighbourhood socio-economic status (SES) on DM survival rates are still not clear, especially in patients of working age. In this paper, we aim to analyze the combined effects of neighbourhood and individual SES on DM survival rates in patients of working age in Taiwan. Methods: The study of 23,781 people who were diagnosed with DM by using population—based study between 2002 and 2006. Each sample was followed up for 4 years or as a sensor case. We defined Individual SES and neighbourhood SES by each patient’s job category and household income which characterized as advantaged or disadvantaged. Then we compared the survival rates by SES group used Cox proportional hazards model for adjust risk factors. Results: The 4-year overall survival rates of diabetic patients were worst for those with low individual SES who living in advantaged neighbourhoods. After adjustment for patient characteristics, DM patients with high individual SES living in disadvantaged neighbourhoods had the same risk of mortality as those patients with high individual SES living in advantaged neighbourhoods (hazard ratio: 1.11; 95% confidence interval [CI]: 0.81–1.51). The study found that DM patients with low individual SES who live in disadvantaged areas had a greater risk of mortality than those with high SES (odds ratio: 2.57; 95% CI: 2.04–3.24). There were significant differences in survival rates between patients with high individual SES and patients with low individual SES. In contrast, the results did not statistically significant differences in survival rates between advantaged and disadvantaged neighbourhood SES groups. Conclusion: DM patients with low individual SES had the worst survival rate, regardless of whether they were living in a high or low SES neighbourhood area. The competitive cause of death, i.e., the fact that complications, rather than DM itself, are often the cause of death, may be the reason for the inverse relationship found between the effects of individual SES and neighbourhood SES on DM survival. We conclude that the socio-economic gradient in survival among DM patients may be the result of differences in access to medical treatment and attributes related to individual SES. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is most common in Southeast Asia. The purpose of this study is to investigate the correlation between wait time and length of radiotherapy and overall survival (OS) of NPC patients in Taiwan.Methods: From Taiwan's National Health Insurance Research Database, this nationwide population-based cohort study identified 3605 NPC patients who received radiotherapy between 2008 and 2011. The impact of time factors on NPC survival rates was estimated with Kaplan-Meier survival curves. A multivariable Cox hazards regression model tested the significance of results after adjustment for other covariables.Results: In all, 317 patients had wait times >4 weeks, 1404 patients had longer duration of radiotherapy (i.e., >10 weeks) and 499 died. Patients with wait times > 4 weeks and length of radiotherapy ≤ 10 weeks didn't have significantly inferior survival. Patients with wait times >4 weeks and length of radiotherapy >10 weeks had significantly lower OS than other groups, with an adjusted hazard ratio of 1.7 (95 % CI, 1.10-2.60).Conclusion: Time was a significant prognostic factor for NPC patients who had both >4 weeks wait times and length of radiotherapy >10 weeks. Patients with wait time > 4 weeks and length of radiotherapy ≤ 10 weeks had a trend toward an inferior survival. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is one of the most common malignant neoplasms in Taiwan. Activation of the mTOR signaling pathway has been linked to decreased radiation responsiveness in human oral cancer, thus it limits efficacy of radiotherapy. To address this question, we investigated the effect of AZD2014, a novel small molecular ATP-competitive inhibitor of mTORC1 and mTORC2 kinase, as a radiosensitizer in primary OSCC and OSCC-derived cell line models. Methods: We isolated primary tumor cells from OSCC tissues and cell lines. AZD2014 was administered with and without ionizing radiation. The radiosensitizing effect of AZD2014 were then assessed using cell viability assays, clonogenic survival assays, and cell cycle analyses. Western blotting was used to detect protein expression. Results: Combination treatment with AZD2014 and irradiation resulted in significant reduction in OSCC cell line and primary OSCC cell colony formation due to the enhanced inhibition of AKT and both mTORC1 and mTORC2 activity. Pre-treatment with AZD2014 in irradiated oral cancer cells induced tumor cell cycle arrest at the G1 and G2/M phases, which led to disruption of cyclin D1-CDK4 and cyclin B1-CDC2 complexes. Moreover, AZD2014 synergized with radiation to promote both apoptosis and autophagy by increasing caspase-3 and LC3 in primary OSCC cells. Conclusions: These findings suggest that in irradiated OSCC cells, co-treatment with AZD2014, which targets mTORC1 and mTORC2 blockade, is an effective radiosensitizing strategy for oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: To understand the impact of socioeconomic status (SES) on the diagnosis of primary open-angle glaucoma (POAG) and primary angle closure glaucoma (PACG) in Taiwan. Methods: Subjects with glaucoma were identified from the National Health Insurance Research Database of year 2006, which included one million randomly selected insurants. Individuals who had ≥4 ambulatory visits within one year which had the diagnosis code of POAG (ICD-9-CM 365.11 or 365.12) or PACG (365.23) and concurrent prescription of anti-glaucoma medication or surgery were selected. Individual SES was represented by monthly income calculated from the insurance premium. Neighborhood SES was defined based on neighborhood household income averages. Urbanization level of habitation was categorized into 3 levels. The odds ratio of having POAG or PACG in subjects with different SES was evaluated by using multiple logistic regression analysis. Results: In total, 752 and 561 subjects with POAG and PACG, respectively, who were treated on a regular basis, were identified. The diagnosis of glaucoma was affected by age, gender, frequency of healthcare utilization, individual SES, and urbanization level of habitation. With the adjustment of age, gender, healthcare utilization, neighborhood SES and level of urbanization, subjects with lower income were more likely to be diagnosed as PACG, but less likely as POAG. Conclusions: Subjects with more frequent healthcare utilization were more likely to be diagnosed with glaucoma. Subjects with low SES were more susceptible to PACG, but subjects with high SES were more likely to be diagnosed as POAG. This information is useful for the design and target participant setting in glaucoma education and screening campaign to maximize the efficacy of limited resources in preventing glaucoma blindness. [ABSTRACT FROM AUTHOR]

Background and Objectives: Pre-dialysis care by a nephrology out-patient department (OPD) may affect the outcomes of patients who ultimately undergo maintenance dialysis. This study examined the effect of pre-dialysis care by a nephrology OPD on the incidence of one-year major cardiovascular events after initiation of dialysis. Design, Setting Participants, & Measurements: The study consisted of Taiwanese patients with chronic kidney disease (CKD) who commenced dialysis from 2006 to 2008. The number of nephrology OPD visits during the critical care period (within 6 months of initiation of dialysis) and the early care period (6–36 months before initiation of dialysis) were analyzed. The primary outcome measure was one-year major cardiovascular events. Results: A total of 1191 CKD patients who initiated dialysis from 2006 to 2008 were included. Binary logistic regression showed that patients with ≧3 visits during the critical care period and those with ≧11 visits during the early care period had fewer composite major cardiovascular events than those with 0 visits. Patients with early referral are less likely to experience composite major cardiovascular events than those with late referral, with aOR 0.574 (95% CI = 0.43–0.77, P<0.001). Patients with both ≧3 visits during critical care period and ≧11 visits during early care period were less likely to experience composite major cardiovascular events (aOR = 0.25, 95% CI = 0.16–0.39, P < 0.001). Conclusions: Patients with adequate pre-dialysis nephrology OPD visits, not just early referral, may had fewer one-year composite major cardiovascular events after initiation of dialysis. This information may be important to medical care providers and public health policy makers in their efforts to improve the well-being of CKD patients. [ABSTRACT FROM AUTHOR]

Background: Identification of patients at risk of death from cancer surgery should aid in preoperative preparation. The purpose of this study is to assess and adjust the age-adjusted Charlson comorbidity index (ACCI) to identify cancer patients with increased risk of perioperative mortality. Methods: We identified 156,151 patients undergoing surgery for one of the ten common cancers between 2007 and 2011 in the Taiwan National Health Insurance Research Database. Half of the patients were randomly selected, and a multivariate logistic regression analysis was used to develop an adjusted-ACCI score for estimating the risk of 90-day mortality by variables from the original ACCI. The score was validated. The association between the score and perioperative mortality was analyzed. Results: The adjusted-ACCI score yield a better discrimination on mortality after cancer surgery than the original ACCI score, with c-statics of 0.75 versus 0.71. Over 80 years of age, 70–80 years, and renal disease had the strongest impact on mortality, hazard ratios 8.40, 3.63, and 3.09 (P < 0.001), respectively. The overall 90-day mortality rates in the entire cohort varied from 0.9%, 2.9%, 7.0%, and 13.2% in four risk groups stratifying by the adjusted-ACCI score; the adjusted hazard ratio for score 4–7, 8–11, and ≥ 12 was 2.84, 6.07, and 11.17 (P < 0.001), respectively, in 90-day mortality compared to score 0–3. Conclusions: The adjusted-ACCI score helps to identify patients with a higher risk of 90-day mortality after cancer surgery. It might be particularly helpful for preoperative evaluation of patients over 80 years of age. [ABSTRACT FROM AUTHOR]

The association between autoimmune diseases and liver cirrhosis has rarely been explored in Asian populations, an endemic area of viral hepatitis. The aim of this study was to investigate the comparative risk of liver cirrhosis among a group of selective autoimmune diseases in Taiwanese patients and to identify groups of high risk. This retrospective study was a nationwide, population-based study and used Taiwan's National Health Insurance Research Database. A total of 29,856 patients with definite diagnosis of selected autoimmune diseases (Registry of Taiwan Catastrophic Illness Database, ACR classification) at the starting time point of January 1, 2005, were enrolled in this study. After tracked for a 5-year period, the endpoints were diagnosis of liver cirrhosis (in accordance with International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM codes 571). The control group was composed of other patients in the same database and consisted of randomly selected 753,495 sex- and age-matched non-autoimmune disease patients. The Cox proportional hazard regression model was used to calculate the risk of liver cirrhosis after adjusting for certain variables such as comorbidity, living area, and socioeconomic status. Among the patients with selected autoimmune diseases, 1987 liver cirrhosis were observed. Patients with psoriasis had a significantly increased risk of liver cirrhosis (HR 1.87, 95 % CI 1.25-2.81) than control group without psoriasis. The risk of liver cirrhosis was significantly lower in patients with rheumatoid arthritis (HR 0.29, 95 % CI 0.19-0.44). There is a gradient of risk of liver cirrhosis among the autoimmune diseases; the specific risks need to be investigated on the basis of hypotheses. Conventional immunosuppressive drug administration should be carefully implemented by regular monitoring of liver condition in order to avoid causing an adverse effect of chronic liver fibrosis. [ABSTRACT FROM AUTHOR]

Background: This nationwide population-based study investigated the risk of cardiovascular diseases after 5-alpha-reductase inhibitor therapy for benign prostate hyperplasia (BPH) using the National Health Insurance Research Database (NHIRD) in Taiwan. Methods: In total, 1,486 adult patients newly diagnosed with BPH and who used 5-alpha-reductase inhibitors were recruited as the study cohort, along with 9,995 subjects who did not use 5-alpha-reductase inhibitors as a comparison cohort from 2003 to 2008. Each patient was monitored for 5 years, and those who subsequently had cardiovascular diseases were identified. A Cox proportional hazards model was used to compare the risk of cardiovascular diseases between the study and comparison cohorts after adjusting for possible confounding risk factors. Results: The patients who received 5-alpha-reductase inhibitor therapy had a lower cumulative rate of cardiovascular diseases than those who did not receive 5-alpha-reductase inhibitor therapy during the 5-year follow-up period (8.4% vs. 11.2%, P=0.003). In subgroup analysis, the 5-year cardiovascular event hazard ratio (HR) was lower among the patients older than 65 years with 91 to 365 cumulative defined daily dose (cDDD) 5-alpha-reductase inhibitor use (HR=0.63, 95% confidence interval (CI) 0.42 to 0.92; P=0.018), however there was no difference among the patients with 28 to 90 and more than 365 cDDD 5-alpha-reductase inhibitor use (HR=1.14, 95% CI 0.77 to 1.68; P=0.518 and HR=0.83, 95% CI 0.57 to 1.20; P=0.310, respectively). Conclusions: 5-alpha-reductase inhibitor therapy did not increase the risk of cardiovascular events in the BPH patients in 5 years of follow-up. Further mechanistic research is needed. [ABSTRACT FROM AUTHOR]

Background: The utility of lymph node ratio (LNR) in predicting outcomes has been reported previously. In current study, we further subgroup by LNR in subjects with lymph nodes metastasis of colorectal cancer, breast cancer, and head and neck cancer. Methods: Cancers with pathological lymph node metastasis (pN+) at time of diagnosis between 2004 and 2012 were identified from the cancer registry database of the Dalin Tzu Chi General Hospital. The Kaplan-Meier method with log-rank test and the Cox proportional hazards model were used to compare the disease-specific survival (DSS) rates for different LNR after adjusting for possible confounding risk factors. Results: A total of 431 cancer patients with pN+ were eligible in the current study: 149 patients with colorectal cancer; 141 patients with breast cancer; and 141 patients with head and neck cancer. High LNR was associated with poor DSS rates with the mean 24-45 months of follow-up period. In the multivariate analysis, high LNR was an independent poor prognostic factor in colorectal cancer (LNR ≥ 0.5; HR 4.10; p < 0.001), breast cancer (LNR ≥ 0.8; HR 5.75; p = 0.002), and head and neck cancer (LNR ≥ 0.4; HR 2.56; p = 0.005). Conclusion: High LNR exerts a significant role as a negative prognostic factor when comparing the traditional American Joint Committee on Cancer (AJCC) lymph nodes classification for major cancers. Therefore, LNR could be considered as an alternative and superior to, at least partially, traditional AJCC lymph nodes classification for cancer patients. [ABSTRACT FROM AUTHOR]

Objectives: To examine the association of individual income and end of life (EOL) care in older cancer decedents in Taiwan. Design: Retrospective cohort study. Setting: National Health Insurance Research Database (NHIRD) in Taiwan. Participants: 28,978 decedents >65 years were diagnosed with cancer and died during 2009-2011 in Taiwan. Of these decedents, 10941, 16535, and 1502 were categorized by individual income as having low, moderate, and high SES, respectively. Main outcome measures: Indicators of aggressiveness of EOL care: chemotherapy use before EOL, more than one emergency department (ER) visit, more than one hospital admission, hospital length of stay >14 days, intensive care unit (ICU) admission, and dying in a hospital. Results: Low individual income was associated with more aggressive EOL treatment (estimate -0.30 for moderate income, -0.27 for high income, both p<0.01). The major source of aggressiveness was the tendency for older decedents with low income to die in the acute care hospital. The indicators had an increasing trend from 2009 to 2011, except for hospital stay >14 days. Conclusions: Low individual income is associated with more aggressive EOL treatment in older cancer decedents. Public health providers should make available appropriate education and hospice resources to these decedents and their families, to reduce the amount of aggressive terminal care such decedents receive. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the impact of comorbidity on survival outcomes for patients with nasopharyngeal carcinoma (NPC) post radiotherapy (RT). Methods: A total of 4095 patients with NPC treated by RT or RT plus chemotherapy (CT) in the period from 2007 to 2011 were included through Taiwan’s National Health Insurance Research Database. Information on comorbidity present prior to the NPC diagnosis was obtained and adapted to the Charlson Comorbidity Index (CCI), Age-Adjusted Charlson Comorbidity Index (ACCI) and a revised head and neck comorbidity index (HN-CCI). The prevalence of comorbidity and the influence on survival were calculated and analyzed. Results: Most of the patients (75%) were male (age 51±13 years) and 2470 of them (60%) had at least one comorbid condition. The most common comorbid condition was diabetes mellitus. According to these three different comorbidity index (CCI, ACCI and HN-CCI), higher scores were associated with worse overall survival (P< 0.001). The Receiver Operating Characteristic (ROC) curve was used to assess the discriminating ability of CCI, AACI and HN-CCI scores and it demonstrated the predictive ability for mortality with the ACCI (0.693, 95% CI 0.670–0.715) was superior to that of the CCI (0.619, 95% CI 0.593–0.644) and HN-CCI (0.545, 95%CI 0.519–0.570). Conclusion: Comorbidities greatly influenced the clinical presentations, therapeutic interventions, and outcomes of patients with NPC post RT. Higher comorbidity index scores accurately was associated with worse survival. The ACCI seems to be a more appropriate prognostic indicator and should be considered in further clinical studies. [ABSTRACT FROM AUTHOR]

Purpose: Radiotherapy with or without chemotherapy is the primary treatment for patients with nasopharyngeal carcinoma (NPC). It wastes time from diagnosis to treatment. Treatment time of radiotherapy generally takes at least seven weeks. The current study aimed to evaluate factors associated with prolonged wait time and longer duration of radiotherapy in NPC patients. Methods and Materials: From Taiwan's National Health Insurance research database, we identified 3,605 NPC patients treated with radiotherapy between 2008 and 2011. Wait time was calculated from the date of diagnosis to the start of radiotherapy. The impact of each variable on wait time and duration of radiotherapy was examined by multilevel analysis using a random-intercept model. Results: The mean wait time and duration of radiotherapy were 1.78±3.33 and 9.72±7.27 weeks, respectively. Multilevel analysis revealed prolonged wait time in patients aged 45–65 years, those receiving radiotherapy alone, those with more comorbidities, those with low SES, and those living in eastern Taiwan. A prolonged duration of radiotherapy was associated with receipt of concurrent chemoradiotherapy, more comorbidities, and moderate SES. Conclusions: Understanding the factors associated with longer wait times and duration of radiotherapy in patients with NPC may help healthcare providers better assist both these patients and potentially those with other head-and-neck cancers. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Recent case reports suggest that zolpidem usage may be associated with infection events. The aim of this study was to determine the risk of infection events in patients with sleep disturbance taking zolpidem in a full 3-year follow-up study. Methods: A total of 17474 subjects with a diagnosis of sleep disturbance in 2002 and 2003 were identified, of whom 5882 had used zolpidem after recruitment. A Cox proportional hazard model was used to estimate the 3-year infection event-free rates for the patients using zolpidem and those not using zolpidem after adjusting for confounding factors. To maximize case ascertainment, only patients hospitalized for infection events were included. Results: A total of 646 patients had had infection events, 331 (5.63%) of whom had been taking zolpidem and 315 (2.71%) had not. Zolpidem usage increased the risk of infection events. After adjustments for gender, age, co-morbidities, and other medications, patients using zolpidem with cDDD 1-28, 29-84, and >84 had hazard ratios of 1.67 (95% CI, 1.32–2.11), 1.91 (95% CI, 1.47–2.49) and 1.62 (95% CI, 1.32–1.98) respectively, compared with patients who did not use zolpidem. Conclusions: Zolpidem increased the risk of infection events in sleep disturbance patients. This increased risk of infection should be explained to sleep disturbance patients, and prescriptions of zolpidem to chronic insomnia patients should be restricted. [Copyright &y& Elsevier]

Background: The purpose of this study was to investigate the incidence and demographic/clinical factors of alanine aminotransferase (ALT) abnormalities at the end of treatment (EOT) in chronic hepatitis C (CHC) patients with sustained virologic response (SVR). Methods and Findings: Seven hundred naïve CHC patients who underwent combination treatment between January 2003 and December 2010 were included in the study. The patients with SVR and serum ALT>upper limit of normal (ULN) at the EOT were further analyzed. The effects of clinical characteristics, treatment regimen, and virologic variables were evaluated by logistic regression. Of the 700 included patients, 488 (69.7%) achieved an SVR after treatment, and 235 (33.6%) had serum ALT levels>ULN at the EOT. Of those 488 patients, 137 (28.1%) had abnormal ALT values at the EOT. A multivariate analysis showed that the occurrence of ALT abnormalities at the EOT was significantly associated with pegylated interferon (PEG-IFN) alfa-2a (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.45–3.45; P<0.001), baseline fatty liver (OR, 1.76; 95% CI, 1.16–2.76; P = 0.007), and baseline liver cirrhosis (OR, 2.35; 95% CI, 1.35–4.09; P = 0.002). Conclusions: Use of PEG-IFN-alfa-2a, fatty liver, and cirrhosis are important factors associated with EOT-ALT abnormality in CHC patients receiving combination therapy that achieve an SVR. PEG-IFN-alfa-2a-related EOT-ALT elevation will become normal at the end of follow-up, but fatty liver and cirrhosis-related ALT elevation will not be resolved. [ABSTRACT FROM AUTHOR]

Background and Purpose: A high risk of stroke occurrence has been reported in several types of irradiated cancer patients. However, clinical data are lacking in irradiated lung cancer patients. The present study intended to explore a risk level of ischemic stroke occurrence in irradiated lung cancer patients. Methods: A nationwide population-based database obtained from the Taiwan National Health Insurance was analyzed. Between 2003 and 2006, we recruited 560 resected lung cancer patients into two study groups: surgery-plus-irradiation (n = 112) and surgery-alone (n = 448). Patients treated with chemotherapy were excluded. Propensity score match was used for pairing cases with a ratio of 1∶4. Two-year ischemic-stroke-free survival was defined as the primary endpoint. Results: Three observations supported a high risk of ischemic stroke occurrence in patients with postoperative irradiation when compared with those patients with surgery alone: first, a high incidence per 1,000 person-year (22.3 versus 11.2, 1.99 folds); second, a low two-year ischemic-stroke-free survival rate (92.2% versus 98.1%, P = 0.019); and third, a high adjusted hazard ratio (HR, 4.19; 95% CI, 1.44–12.22; P = 0.009). More notably, the highest risk of ischemic stroke occurrence was found in irradiated patients who had diabetes mellitus (HR, 34.74; 95% CI, 6.35->100; P<0.0001). Conclusions: A high incidence of ischemic stroke was observed in irradiated lung cancer patients, especially in those with diabetes mellitus. For these patients, close clinical surveillance and strict diabetes control should be considered. Further studies to define detail biological mechanisms are encouraged. [ABSTRACT FROM AUTHOR]